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The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST)
Fertility and Sterility ( IF 6.7 ) Pub Date : 2021-10-14 , DOI: 10.1016/j.fertnstert.2021.09.009
Tim Jenkins 1 , Kenneth Aston 2 , Douglas Carrell 3 , Elizabeth DeVilbiss 4 , Lindsey Sjaarda 4 , Neil Perkins 5 , James L Mills 4 , Zhen Chen 5 , Amy Sparks 6 , Traci Clemons 7 , Kayla Chaney 7 , C Matthew Peterson 8 , Benjamin Emery 9 , Jim Hotaling 10 , Erica Johnstone 8 , Enrique Schisterman 11 , Sunni L Mumford 4
Affiliation  

Objective

To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns.

Design

A multicenter, double-blind, block randomized, placebo-controlled trial titled “The Folic Acid and Zinc Supplementation Trial (FAZST).”

Setting

Infertility care centers.

Patient(s)

Male partners (18 years and older) from heterosexual couples (female partners aged 18–45 years) seeking fertility treatment were recruited.

Intervention(s)

Men were randomized 1:1 to receive folic acid (5 mg) and elemental zinc (30 mg) (n = 713) or a matching placebo (n = 757) daily for 6 months.

Main Outcome Measure(s)

Sperm DNA methylation was analyzed using the EPIC methylation array (Illumina) at 6 months. Differential sperm DNA methylation was assessed at multiple levels (regional, single cytosine phosphate guanine, etc.). We additionally assessed the impact of supplementation on epigenetic age.

Result(s)

No significant differences were identified between the treatment and placebo groups although some trends appeared to be present. To determine if these trends were noteworthy, we implemented various permutations and found that the patterns we identified were no more than would be expected by random chance.

Conclusion(s)

The data presented here strongly suggest that this supplementation regimen is not effective at altering sperm DNA methylation. These data comport well with previous findings from the FAZST study that found no impact of supplementation on basic semen analysis parameters or live birth.

Clinical Trial Registration Number

ClinicalTrials.gov Identifier: NCT01857310.



中文翻译:

锌和叶酸补充剂对精子 DNA 甲基化的影响:叶酸和锌补充剂随机临床试验 (FAZST) 的结果

客观的

确定 6 个月的叶酸(5 毫克)和锌(30 毫克)补充剂是否会影响精子 DNA 甲基化模式。

设计

一项名为“叶酸和锌补充剂试验 (FAZST)”的多中心、双盲、区组随机、安慰剂对照试验。

环境

不孕不育护理中心。

患者)

招募了寻求生育治疗的异性恋夫妇(18-45 岁的女性伴侣)的男性伴侣(18 岁及以上)。

干预措施

男性以 1:1 的比例随机接受叶酸(5 毫克)和元素锌(30 毫克)(n = 713)或匹配的安慰剂(n = 757),持续 6 个月。

主要观察指标)

在 6 个月时使用 EPIC 甲基化阵列 (Illumina) 分析精子 DNA 甲基化。在多个水平(区域、单胞嘧啶磷酸鸟嘌呤等)评估差异精子 DNA 甲基化。我们还评估了补充剂对表观遗传年龄的影响。

结果)

尽管似乎存在一些趋势,但治疗组和安慰剂组之间没有发现显着差异。为了确定这些趋势是否值得注意,我们实施了各种排列,发现我们确定的模式并不比随机机会预期的要多。

结论

这里提供的数据强烈表明这种补充方案在改变精子 DNA 甲基化方面无效。这些数据与 FAZST 研究的先前发现非常吻合,该研究发现补充对基本精液分析参数或活产没有影响。

临床试验注册号

ClinicalTrials.gov 标识符:NCT01857310。

更新日期:2021-10-14
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